Search Results (448)

Ischemic stroke is now widely recognized as a disease with a strong inflammatory profile. Cerebral vascular damage is both preceded and followed by a chain of molecular events involving immune cells and inflammatory markers, irrespective of the etiology of the ischemic injury. Over time, an increasingly comprehensive understanding of these markers has led to a better insight into the mechanisms behind the vascular event and recovery following ischemic stroke. However, to date, there are still no available circulating or tissue biomarkers for early diagnosis or prognostic stratification, making ischemic stroke diagnosis contingent on clinical and instrumental investigations. However, neurological and internal medicine research is progressing in identifying markers that could potentially take on this role. This manuscript, therefore, aims to review the most recent and innovative results of medical advances, summarising the current state of the art and future perspectives. If ischaemic stroke is an inflammatory disease, it is also true that it is not just a singular condition, but a group of entities with their own neuroinflammatory features. Thus, given that, in ischemic cerebral vascular damage, “time is brain,” tracking increasingly accurate markers in the diagnosis of ischemic stroke is a valuable tool that will potentially enable earlier recognition of this disease and, hopefully, make it less disabling and more widely treated. Full article

Arrhythmogenic cardiomyopathy (ACM; MIM #107970) is a primitive heart muscle disease characterized by progressive myocardial loss and fibrosis or fibrofatty replacement, predisposing patients to ventricular arrhythmias, sudden cardiac death, and heart failure. Despite advances in imaging and genetics, early diagnosis remains challenging due to incomplete penetrance, variable phenotypic expressivity, and the fact that fatal arrhythmic events may often occur in the early stages of the disease. In this context, the identification of reliable biomarkers could enhance diagnostic accuracy, support risk stratification, and guide clinical management. This narrative review examines the current landscape of potential and emerging biomarkers in ACM, including troponins, natriuretic peptides, inflammatory proteins, microRNAs, fibrosis-related markers, and other molecules. Several of these biomarkers have demonstrated associations with disease severity, arrhythmic burden, or structural progression, although their routine clinical utility remains limited. The increasing relevance of genetic testing and non-invasive tissue characterization—particularly through cardiac imaging techniques—should also be emphasized as part of a multimodal diagnostic strategy in which biomarkers may play a complementary role. Although no single biomarker currently meets the criteria for a standalone diagnostic application, ongoing research into multi-marker panels and novel molecular targets offers promising perspectives. In conclusion, the integration of circulating biomarkers with imaging findings, genetic data, and clinical parameters may open new avenues for improving early detection and supporting personalized therapeutic strategies in patients with suspected ACM. Full article

Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular risk characterized by low-grade inflammation. The aim of this systematic review and meta-analysis was to assess the effects of resistance exercise training (RET) predominantly on cytokines, along with changes in glucose profile and body composition in T2DM patients. The present systematic review and meta-analysis was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library databases from their inception up to July 2024 (PROSPERO; registration number CRD420251149352). We screened only for randomized controlled trials investigating the effects of systematic, supervised RET on C-reactive protein (CRP) and adipokines: adiponectin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls. Sixteen studies involving a total of 668 T2DM patients were retrieved from the databases for meta-analysis. We used the GRADE framework for assessing the certainty of evidence. Cochran Q-score (I²) was used to estimate heterogeneity among studies (level of significance p < 0.10) and risk of bias analysis was also performed. The cumulative results showed that post-RET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L) (WMD: −0.63; 95%CIs: −1.05, −0.20; p < 0.001); adiponectin (μg/mL) (WMD: −0.94; 95%CIs: −1.49, −0.38; p < 0.001). The results from adiponectin are quite conflicting since they derived from only three studies, where one of them had the greater impact. In parallel, we noticed significant amelioration of fasting glucose and HbA1c (p < 0.001), while body weight remained unaltered. Our meta-analysis demonstrated non-significantly lower levels of IL-6 and TNF-α in RET vs. control group. RET can merely reduce the inflammatory burden in T2DM patients by ameliorating the circulating levels of CRP and adiponectin, while in the rest of the biomarkers, non-significant results were obtained. Hence, the overall clinical impact of those anti-inflammatory effects of RET needs to be determined. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disease with heterogeneous clinical manifestations and uncertain systemic immune involvement. This study aimed to characterize peripheral immune profiles and circulating tumor markers in women with ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE), and to explore their associations with disease severity, symptom burden, and physical health perception. Peripheral blood leukocyte subsets, plasma cytokines, and tumor markers (CA125, CA19-9, CEA, HE4) were analyzed in 146 patients and 50 healthy controls. OE was associated with increased monocyte counts and reduced neutrophil proportions, while DIE showed elevated levels of IL-8 and Galectin-1. IL-33 levels correlated negatively with the revised American Society for Reproductive Medicine (rASRM) scores and positively with neutrophil proportion, suggesting a role in systemic immune regulation. Tumor marker levels varied by subtype: CA19-9 was higher in OE, and CEA in DIE. CA125 correlated with disease severity, and CEA with monocyte levels. Exploratory heatmaps revealed consistent immune-tumor associations linked to anatomical severity and symptom profiles. Although exploratory, these findings highlight the presence of distinct systemic immune patterns in endometriosis and support the potential of integrative blood-based biomarkers for future diagnostic and stratification strategies. Full article

Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40–60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients’ selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) investigate whether whole blood counts, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), serum adiponectin levels, and the mRNA expression of inflammatory genes (TLR2, TLR4, pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, anti-inflammatory cytokines: IL-1RA, IL-10, and adiponectin) in VAT are altered in women with GDM in comparison to pregnant women with normal glucose tolerance (NGT), and (2) determine the correlations between systemic and local VAT inflammation in all, GDM, and NGT women. Methods: Study of 50 GDM and 50 women with NGT with a cross-sectional design. Standard biochemical and hematological tests were conducted and relative mRNA expression in VAT was measured by RT-qPCR. Results: Women with GDM showed higher neutrophil, monocyte, NLR, MLR, and VAT TNF-α/IL-10 mRNA expression ratios while lymphocyte and eosinophil counts, serum adiponectin, and mRNA local VAT inflammatory markers such as TLR2, TLR4, IL-1β, IL-6, IL-1RA, and IL-10 were lower in women with GDM relative to women with NGT. Additionally, the circulating monocyte count were associated with TLR2 and TLR-4 VAT mRNA expression levels and eosinophils count were associated with IL-1β, IL-6, IL-10, and IL-1RA VAT expression levels in women with GDM. Conclusions: GDM is characterized by systemic inflammation, and some circulating immune cells, such as monocytes and eosinophils, are associated with the expression of inflammatory markers in VAT. Full article

Background/Objectives: Exogenous ketone supplements elevate circulating ketones without carbohydrate restriction, but their long-term hepatic safety remains unclear. This study evaluated the formulation-dependent impact of chronic ketone supplementation on liver histopathology, inflammatory signaling, and systemic biomarkers in rats. Methods: Male Sprague-Dawley rats were orally administered 1,3-butanediol (BD), medium-chain triglycerides (MCTs), ketone ester (KE), ketone electrolytes/salts (KSs), or a ketone salt–MCT combination (KSMCT) for 4 weeks. In a separate arm, animals received standard diet (SD), or SD supplemented with low-dose KE (LKE) or high-dose KE (HKE), for 83 days. Liver structure was assessed by hematoxylin and eosin staining with quantification of red blood cell density and lipid accumulation. Inflammatory and metabolic responses were evaluated by TNF-α and arginase immunohistochemistry. Serum biochemistry included glucose, proteins, electrolytes, and liver and kidney function markers. Results: BD and KE induced macrovesicular steatosis, vascular congestion, and elevated TNF-α and arginase expression, consistent with hepatic stress. MCT caused moderate hepatocellular ballooning and lipid deposition, whereas KS preserved near-normal hepatic morphology. KSMCT produced intermediate effects, reducing lipid accumulation and TNF-α compared with MCT or KE alone. KE supplementation caused dose-dependent reductions in globulin and elevations in creatinine, while HKE reduced sodium and glucose levels. Conclusions: Chronic hepatic responses to exogenous ketones are highly formulation dependent. KS demonstrated the most favorable safety profile under the tested conditions, maintaining normal hepatic structure, while BD and KE elicited adverse changes. Formulation choice is critical for the safe long-term use of exogenous ketones. Full article

Background: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting large and medium-sized arteries, predominantly in individuals over 50 years. While it traditionally involves cranial branches of the external carotid artery, particularly the temporal arteries, growing evidence underscores frequent extracranial involvement, especially in the supra-aortic trunks. Objective: We aimed to critically review the diagnostic utility of extended Color Doppler Ultrasound (CDUS) in GCA, with a focus on vertebrobasilar involvement and current international imaging guidelines. Methods: Taking inspiration from a representative case of extracranial GCA with vertebrobasilar ischemic events, the current literature and international recommendations (e.g., EULAR, ACR, BSR and SIR) were reviewed. Results: Diagnostic accuracy significantly improves when CDUS is extended to include carotid, vertebral, subclavian and axillary arteries. Elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) correlate with large-vessel involvement and support the use of extended scanning protocols. International guidelines vary in their emphasis on extended CDUS, but consensus is growing toward ultrasound imaging-first strategies in expert hands. Conclusion: Extended CDUS is a sensitive, non-invasive first-line diagnostic tool for GCA. In patients with symptoms of the posterior cerebral circulation and elevated inflammatory indices, early comprehensive vascular imaging reduces diagnostic delay and may obviate the need for temporal artery biopsy. Full article

Allograft inflammatory factor-1 (AIF1) is a conserved calcium-binding protein involved in inflammatory and neuro-immune responses and expressed in Pomacea canaliculata (Pc-AIF1) during cephalic tentacle regeneration. Here, we investigated the expression and distribution of Pc-AIF1 in control conditions and during cephalic tentacle regeneration. A transcriptomic analysis of 315 RNA-seq datasets revealed maximal Pc-AIF1 expression in circulating hemocytes and hemocyte-rich tissues. Pc-AIF1 was also highly expressed in neural ganglia. Fluorescence in situ hybridization (FISH) evidenced Pc-AIF1 in circulating hemocytes and in the phagocytic hemocyte aggregates in the posterior kidney. qPCR showed the constitutive expression of Pc-AIF1 in cerebral ganglia. FISH experiments showed Pc-AIF1-positive cells within the cephalic tentacle blastema at 24 h post-amputation (hpa). Even if the amputation left them untouched, both the ipsilateral and contralateral cerebral ganglia increased Pc-AIF1 expression until 48 hpa. Immunocytochemical experiments evidenced positive cells to RCA120 (a microglial marker in mammals) among circulating hemocytes, in the connective tissue surrounding the cerebral ganglia, and within the regenerating tentacles. These findings suggest that Pc-AIF1 is a neuro-immune marker constitutively expressed in hemocyte populations and neural tissues; it is associated with the immediate hemocyte response to wounding and the neuro-immune interplay during the regeneration of sensory organs. Full article

Background/Objectives: Cottonseed oil (CSO) is a dietary oil especially high in the n-6 polyunsaturated fatty acid (PUFA), linoleic acid (FA 18:2), which is a precursor for many pro-inflammatory eicosanoids. Curiously, diets rich in CSO have not been shown to cause increases in inflammatory markers or other negative health outcomes in humans. To rigorously test this, we have compared the health impact of a diet rich in CSO to olive oil (OO), which is generally considered to be a healthy oil. Methods: Specifically, this study examines circulating metabolite and lipid profiles during a 4-week dietary intervention with CSO or OO on 47 healthy adults. Untargeted metabolomics, targeted bulk lipidomics, and targeted lipid mediator analyses were conducted on fasting plasma samples taken pre- and post-dietary intervention. Results: A high degree of similarity was observed in the global metabolomic profiles of CSO and OO participants, indicating that CSO may elicit metabolic responses comparable to those of OO, potentially supporting similar effects on metabolic health markers. Targeted bulk lipidomics revealed changes in acyl chain composition reflective of the dominant fatty acid consumed—either 18:2 in CSO or 18:1 in OO. Immunoregulatory lipids 15-deoxy-PGJ2 and prostaglandin F2 alpha (PGF2a) were both higher in abundance in high-CSO diets, demonstrating differential effects of CSO and OO on immunoregulatory compounds. A correlative network analysis revealed two clusters arising from the dietary intervention as drivers of the dietary and immune responses. Conclusions: This study shows that CSO and OO differentially impact the circulating lipidome and immunoregulatory compounds in healthy adults. Full article

Background/Objectives: Chronic particulate matter 2.5 (PM2.5) exposure is associated with vascular inflammation and cardiovascular risk. However, the role of diet in modulating inflammation under such conditions remains unclear. This study explored the associations between nutrient intake and circulating vascular inflammatory biomarkers among apparently healthy adults living in PM2.5-affected rural and peri-urban areas in Chiang Mai Province, Thailand. Methods: Fifty-three healthy adults (27 rural; 26 peri-urban) were assessed for sociodemographic characteristics, clinical parameters, and dietary intake using three consecutive 24 h recalls. Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and interleukin-6 (IL-6) were measured. Multiple linear regression was used to analyze associations between nutrient intake and inflammatory markers, adjusting for potential confounders. Results: Peri-urban participants exhibited significantly higher levels of ICAM-1, VCAM-1, and IL-6 compared to rural participants (p < 0.05). They also had higher intakes of sugars and saturated fatty acids, whereas rural participants consumed more cholesterol, antioxidant nutrients (vitamins C, A, and E), and minerals (e.g., potassium, selenium). Regression analyses revealed positive associations between sugar intake and all three inflammatory markers (ICAM-1: β = 0.467; VCAM-1: β = 0.481; IL-6: β = 0.557; all p ≤ 0.001). In contrast, intakes of selenium and vitamin A were inversely associated with VCAM-1 levels. Conclusions: These findings suggest that certain dietary components may influence vascular inflammation among individuals exposed to PM2.5. Encouraging consumption of anti-inflammatory nutrients may help mitigate pollution-related cardiovascular risks. Full article

Background/Objectives: Chronic exercise training reduces markers of systemic inflammation; however, less is known about how to optimize this adaptation using nutrition. Dairy products, especially fermented ones, like Greek yogurt (GY), contain anti-inflammatory constituents. This secondary analysis aimed to examine the influence of post-exercise GY consumption vs. an isoenergetic carbohydrate pudding (CP; control) on markers of systemic inflammation during an exercise training intervention. Methods: Thirty healthy young males completed 12 weeks of resistance and plyometric exercise training and were randomized to consume GY (n = 15) or CP (n = 15). Rested/fasted blood samples were acquired at baseline, and weeks 1 and 12, and inflammatory biomarkers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, IL-1 receptor antagonist [IL-1ra], IL-1Beta [IL-1β], IL-10, and C-reactive protein [CRP]) were measured. Linear mixed models were run on the absolute concentrations, and linear regressions were performed on the absolute change (baseline to week 12), allowing us to account for important covariates. Results: In both groups, CRP (pro) and IL-1ra (anti) increased at week 1 vs. baseline and week 12, while IL-1β (pro) decreased at week 12 vs. baseline (main time effects). We observed significant interactions for IL-6, TNF-α, and the TNF-α/IL-10 ratio, indicating that at week 12, IL-6 (pro) was lower in GY, whereas TNF-α and TNF-α/IL-10 (both pro-inflammatory) were higher in CP vs. week 1 and baseline, respectively. Additionally, within our linear regression models, higher baseline concentrations of IL-1ra (anti), IL-10 (anti) and CRP (pro) predicted greater change over the intervention. Conclusions: These results indicate that our intervention benefited circulating inflammatory markers, and GY supplementation may enhance these effects. Full article

An increasing body of evidence suggests the likelihood of a link between arterial atherosclerotic disease (AAD) and venous thromboembolic disease (VTED). Inflammation is accepted as a basic pathogenetic mechanism of both diseases. The involvement of inflammation in the pathogenesis of AAD and VTED is supported by increased levels of circulating inflammatory markers, particularly interleukins, which are involved in the development and progression of atherosclerosis as well as in thrombus formation in arterial and venous beds. A consideration supporting a close link between these diseases is also based on the evidence of common risk factors which promote the development of both diseases through stimulation of systemic inflammation. Further, the relationship between arterial and VTED is supported by findings of the simultaneous appearance of clinical or preclinical AAD and VTED. The aim of this narrative review is to report evidence of the inflammatory basis of arterial and venous diseases, which is important for common therapeutic procedures. Besides classical drugs used in the prevention of arterial and venous diseases with their pleotropic anti-inflammatory activity, new anti-inflammatory drugs provide the possibility for treatment of both AAD and VTED and could represent a unified therapeutic approach to both diseases. Full article

Circulating microRNAs (miRNAs) have emerged as non-invasive biomarkers that may be associated with cancer risk, but their role in the development of colon cancer is still not well understood. We conducted a nested case-control study within the EPIC-Italy cohort to investigate the association between pre-diagnostic serum levels of eight candidate miRNAs (Let7, Mir21, Mir155, Mir181, Mir222, Mir145, Mir92, and Mir20) and subsequent colon cancer occurrence. A total of 104 incident colon cancer cases were matched to 104 controls by center, sex, age, recruitment date, and vital status. miRNA expression was quantified using RT-qPCR and normalized to Mir484. Logistic regression models were applied to estimate odds ratios, 95% confidence intervals, and p-values, adjusting for age at recruitment, smoking status, body mass index, physical activity, adherence to a Mediterranean diet, and socioeconomic position. Elevated expression of Let7 (OR = 0.91; 95% CI: 0.84–1.00; p = 0.04) was associated with slightly lower odds of colon cancer in unadjusted models. Mir21 and Mir222 showed borderline associations (p = 0.07 and p = 0.09, respectively), but these did not remain significant after Bonferroni correction. This result was consistent in the multivariate logistic model: higher levels of Let7 (OR = 0.91; 95% CI: 0.82–1.00; p = 0.06) and Mir222 (OR = 0.75; 95% CI: 0.57–1.00; p = 0.05) are suggestive of an association with lower odds of colon cancer. Our findings highlight the challenges of using circulating miRNAs as very early biomarkers, particularly when samples are collected nearly a decade before diagnosis. Future studies with larger sample sizes, serial blood collections, and integration with inflammatory and immune markers will be crucial to clarify the temporal dynamics of circulating miRNA alterations and their potential role in risk-adapted screening strategies. Full article

Background/Objectives: Gut microbial dysbiosis, leaky gut, and increased transepithelial translocation of commensal bacteria have been documented in multiple sclerosis (MS). Intrathecal IgGs specific for Akkermansia muciniphila, a gut bacterium, are increased in patients with MS and associated with clinical disability. Our objective here was to explore the putative involvement of intrathecal anti-A. muciniphila IgG in MS pathogenesis by characterizing patients with different anti-A. muciniphila IgG indices. Methods: Serum and intrathecal IgG specific for A. muciniphila and other gut bacteria, as well as routine cerebrospinal fluid (CSF) parameters, were measured in 61 patients with MS. Examination of these patients included immunophenotyping of CSF-infiltrating and paired circulating lymphocytes, intrathecal markers of neurodegeneration and inflammation, and a detailed characterization of demographic, clinical, and magnetic resonance imaging (MRI) features. Results: Plasma blasts (p < 0.01), B cells (p < 0.01), and Th2 cells (p < 0.01), which might be involved in antibody production, were increased in the CSF of these patients, as well as blood pro-inflammatory Th17 cells (p < 0.05). Anti-A. muciniphila IgG indices were negatively associated with blood-brain barrier (BBB) permeability and circulating monocytes (p < 0.001), and positively with brain lesion load (p < 0.01). Conclusions: The differences between patients with low and high anti-A. muciniphila IgG indexes regarding BBB permeability, CSF cell infiltrates, and pro-inflammatory peripheral immune cells, as well as imaging features, support a role of anti-A. muciniphila immune response in MS pathogenesis. Full article